diff --git a/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/instrument.mjs b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/instrument.mjs
new file mode 100644
index 000000000000..46a27dd03b74
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/instrument.mjs
@@ -0,0 +1,9 @@
+import * as Sentry from '@sentry/node';
+import { loggingTransport } from '@sentry-internal/node-integration-tests';
+
+Sentry.init({
+  dsn: 'https://public@dsn.ingest.sentry.io/1337',
+  release: '1.0',
+  tracesSampleRate: 1.0,
+  transport: loggingTransport,
+});
diff --git a/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/scenario.mjs b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/scenario.mjs
new file mode 100644
index 000000000000..aa9a5186fc82
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/scenario.mjs
@@ -0,0 +1,15 @@
+// `mysql2` >= 3.20 has a registration-only orchestrion config (its tracing
+// channels are native, so orchestrion doesn't wrap it — it only splices a
+// module-registration snippet). Requiring `mysql2` loads its instrumented file
+// (`lib/base/connection.js`), which drives the runtime module hook to transform
+// it.
+//
+// The registration-only transform is wired into the bundler plugins only, so
+// before the runtime instrumentation set excluded these configs, the runtime
+// hook threw `TypeError: transform is not a function`, which the loader turned
+// into an always-on "`@sentry/server-runtime-injection` was bundled ..." warning
+// on stderr. `ensureNoErrorOutput` fails the test if that warning (or anything
+// else) reaches stderr.
+//
+// A bare `import` is service-free — it never connects to a database.
+await import('mysql2');
diff --git a/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/test.ts b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/test.ts
new file mode 100644
index 000000000000..6aa84f71fa74
--- /dev/null
+++ b/dev-packages/node-integration-tests/suites/tracing/orchestrion-registration-only/test.ts
@@ -0,0 +1,24 @@
+import * as path from 'path';
+import { afterAll, describe, test } from 'vitest';
+import { cleanupChildProcesses, createRunner } from '../../../utils/runner';
+
+afterAll(() => {
+  cleanupChildProcesses();
+});
+
+describe('orchestrion registration-only modules at runtime', () => {
+  // A registration-only config (a native-channel library such as `mysql2` >= 3.20)
+  // carries the custom `MODULE_REGISTRATION_TRANSFORM`, which is wired into the
+  // bundler plugins only. The runtime loader excludes these
+  // (`SENTRY_RUNTIME_INSTRUMENTATIONS`), so loading such a module must not attempt
+  // an unavailable transform — which would surface as `TypeError: transform is
+  // not a function` and the always-on "`@sentry/server-runtime-injection` was
+  // bundled ..." warning on stderr. `ensureNoErrorOutput` fails on any stderr.
+  test('loads a native-channel library without the transformer-unavailable warning', async () => {
+    await createRunner(__dirname, 'scenario.mjs')
+      .withInstrument(path.join(__dirname, 'instrument.mjs'))
+      .ensureNoErrorOutput()
+      .start()
+      .completed();
+  });
+});
diff --git a/packages/server-runtime-injection/src/register.ts b/packages/server-runtime-injection/src/register.ts
index 7c437e2980c0..9d130ab41c53 100644
--- a/packages/server-runtime-injection/src/register.ts
+++ b/packages/server-runtime-injection/src/register.ts
@@ -3,7 +3,7 @@ import { existsSync } from 'node:fs';
 import * as Module from 'node:module';
 import { dirname, join } from 'node:path';
 import { fileURLToPath, pathToFileURL } from 'node:url';
-import { SENTRY_INSTRUMENTATIONS } from '@sentry/server-utils/orchestrion/config';
+import { SENTRY_RUNTIME_INSTRUMENTATIONS } from '@sentry/server-utils/orchestrion/config';
 import type { register } from 'node:module';
 import ModulePatch from '@apm-js-collab/tracing-hooks';
 import { initialize, load, resolve, createDiagnosticsPort } from '@apm-js-collab/tracing-hooks/hook-sync.mjs';
@@ -164,7 +164,7 @@ export function registerDiagnosticsChannelInjection(): void {
   // incompatibility) we warn and continue without channel injection.
   try {
     if (typeof mod.registerHooks === 'function' && stableSyncHooks) {
-      initialize({ instrumentations: SENTRY_INSTRUMENTATIONS });
+      initialize({ instrumentations: SENTRY_RUNTIME_INSTRUMENTATIONS });
       mod.registerHooks({ resolve, load });
       debug.log('Registered diagnostics-channel injection via Module.registerHooks()');
     } else if (typeof mod.register === 'function' && !globalAny.Bun && !globalAny.Deno) {
@@ -223,7 +223,7 @@ export function registerDiagnosticsChannelInjection(): void {
 
       mod.register(hookSpecifier, {
         parentURL,
-        data: { instrumentations: SENTRY_INSTRUMENTATIONS, diagnosticsPort },
+        data: { instrumentations: SENTRY_RUNTIME_INSTRUMENTATIONS, diagnosticsPort },
         transferList: [diagnosticsPort],
       });
 
@@ -232,7 +232,7 @@ export function registerDiagnosticsChannelInjection(): void {
       // are resolved through the CJS machinery and never reach the ESM
       // register hook, so without this patch the file we want to instrument
       // loads untransformed.
-      new ModulePatch({ instrumentations: SENTRY_INSTRUMENTATIONS }).patch();
+      new ModulePatch({ instrumentations: SENTRY_RUNTIME_INSTRUMENTATIONS }).patch();
       debug.log('Registered diagnostics-channel injection via Module.register()');
     } else {
       marker.runtimeUnavailable = true;
diff --git a/packages/server-utils/src/orchestrion/config/index.ts b/packages/server-utils/src/orchestrion/config/index.ts
index 1fec4fb2c5ad..271f13600536 100644
--- a/packages/server-utils/src/orchestrion/config/index.ts
+++ b/packages/server-utils/src/orchestrion/config/index.ts
@@ -81,6 +81,38 @@ export const SENTRY_INSTRUMENTATIONS: InstrumentationConfig[] = [
   ...vercelAiConfig,
 ];
 
+/**
+ * The subset of {@link SENTRY_INSTRUMENTATIONS} the RUNTIME loader
+ * (`@sentry/server-runtime-injection`'s `register`, reached via `--import` or
+ * `Sentry.init()`) can actually apply.
+ *
+ * Registration-only configs (native-channel libraries such as `ai` v7,
+ * `ioredis`, `@redis/client`, `mysql2`, `mongoose`) carry the custom
+ * `MODULE_REGISTRATION_TRANSFORM` operator. That operator is wired into the
+ * BUNDLER plugins only (see `orchestrion/bundler/moduleInjectedTransform.ts`,
+ * applied via `bundler/options.ts`'s `customTransforms`); the runtime loader's
+ * `initialize()` receives no custom transforms. Attempting one of these at
+ * runtime therefore throws `TypeError: transform is not a function`, which the
+ * loader misreports as the always-on "`@sentry/server-runtime-injection` was
+ * bundled ... loads uninstrumented" warning even though nothing is wrong.
+ *
+ * Excluding them at runtime is correct, not just a way to silence the warning:
+ * these libraries publish their own tracing channels, and their integrations
+ * subscribe through `setupOnce()` / `waitForTracingChannelBinding`,
+ * independently of the module-injected snippet. That snippet only fires
+ * `orchestrion.module-injected`, which drives the `setup()` /
+ * `invokeOrchestrionInstrumentation` path; for a native-channel version that
+ * path subscribes to the injected `orchestrion:*` channels the library never
+ * publishes — a no-op. So running these at runtime would add no spans. The
+ * snippet earns its keep only on the BUNDLER path — notably bundler-only SDKs
+ * (e.g. `@sentry/cloudflare`) that discover a loaded module via that event to
+ * instantiate its integration factory. `@sentry/node` registers its
+ * integrations statically, so it does not need it.
+ */
+export const SENTRY_RUNTIME_INSTRUMENTATIONS: InstrumentationConfig[] = SENTRY_INSTRUMENTATIONS.filter(
+  config => !config.transform,
+);
+
 /**
  * The unique set of package names instrumented by `SENTRY_INSTRUMENTATIONS`
  * merged with any caller-provided `instrumentations` (e.g. `['mysql']`).
diff --git a/packages/server-utils/test/orchestrion/config.test.ts b/packages/server-utils/test/orchestrion/config.test.ts
index ae5899cafdb4..73fc5167b86f 100644
--- a/packages/server-utils/test/orchestrion/config.test.ts
+++ b/packages/server-utils/test/orchestrion/config.test.ts
@@ -4,9 +4,11 @@ import {
   INSTRUMENTED_MODULE_NAMES,
   instrumentedModuleNames,
   SENTRY_INSTRUMENTATIONS,
+  SENTRY_RUNTIME_INSTRUMENTATIONS,
   withoutInstrumentedExternals,
 } from '../../src/orchestrion/config';
 import { CHANNEL_INTEGRATION_DEFINITIONS } from '../../src/orchestrion/config/channel-integration-definitions';
+import { MODULE_REGISTRATION_TRANSFORM } from '../../src/orchestrion/config/registration-only';
 
 describe('orchestrion config — scoped @hapi/hapi module', () => {
   it('includes the scoped @hapi/hapi name in INSTRUMENTED_MODULE_NAMES', () => {
@@ -55,3 +57,51 @@ describe('orchestrion config — custom instrumentations', () => {
     expect(withoutInstrumentedExternals(external)).toEqual(['react', 'my-lib']);
   });
 });
+
+describe('orchestrion config — SENTRY_RUNTIME_INSTRUMENTATIONS', () => {
+  // The runtime loader has no custom transforms, so a registration-only config
+  // (its `transform` is the bundler-only `MODULE_REGISTRATION_TRANSFORM`) throws
+  // `transform is not a function` there. These are excluded from the runtime set;
+  // the bundler keeps the full `SENTRY_INSTRUMENTATIONS`.
+  it('only keeps configs the transform-less runtime loader can actually apply', () => {
+    // The filter is only meaningful if some configs carry a custom transform to drop.
+    expect(SENTRY_INSTRUMENTATIONS.some(c => c.transform)).toBe(true);
+
+    // The invariant: the runtime loader registers no custom transforms, so any config
+    // carrying one (not just MODULE_REGISTRATION_TRANSFORM) throws there. Every runtime
+    // config must therefore be transform-less — this is what we need to hold even if a
+    // future feature adds a different named transform.
+    expect(SENTRY_RUNTIME_INSTRUMENTATIONS.every(c => !c.transform)).toBe(true);
+  });
+
+  it('keeps every transform-less config, dropping only the ones with a custom transform', () => {
+    // Nothing the runtime can apply is lost: each transform-less config from the full
+    // set survives (by reference), and the runtime set adds nothing extra.
+    for (const config of SENTRY_INSTRUMENTATIONS.filter(c => !c.transform)) {
+      expect(SENTRY_RUNTIME_INSTRUMENTATIONS).toContain(config);
+    }
+    expect(SENTRY_RUNTIME_INSTRUMENTATIONS).toHaveLength(SENTRY_INSTRUMENTATIONS.filter(c => !c.transform).length);
+  });
+
+  it('excludes only the native-channel modules, and only via their registration-only config', () => {
+    const registrationOnlyModules = [
+      ...new Set(
+        SENTRY_INSTRUMENTATIONS.filter(c => c.transform === MODULE_REGISTRATION_TRANSFORM).map(c => c.module.name),
+      ),
+    ].sort();
+
+    // These native-channel libraries are known to use a registration-only config
+    // today. Asserted as a subset (not the exact set) so adding another such
+    // library does not break this test.
+    expect(registrationOnlyModules).toEqual(
+      expect.arrayContaining(['@redis/client', 'ai', 'ioredis', 'mongoose', 'mysql2']),
+    );
+
+    // The exclusion is per-config, not per-module: a module with both a
+    // registration-only (native) config and older transform-based configs keeps
+    // the latter at runtime. `ai` (v7 native + v4–6 transforms) is one such case.
+    const runtimeAiConfigs = SENTRY_RUNTIME_INSTRUMENTATIONS.filter(c => c.module.name === 'ai');
+    expect(runtimeAiConfigs.length).toBeGreaterThan(0);
+    expect(runtimeAiConfigs.every(c => !c.transform)).toBe(true);
+  });
+});