What is your anti-virus software?

Only the built in win defender (win 11, home), nothing additional.

Try to start Windows 10 in safe mode with networking enabled.

Still in Windows safe mode, start Thunderbird in safe mode. Does the problem go away?

Windows safe mode disables anti-virus software. This is a troubleshooting step, not a solution.

I was able to mimic a solution by disabling defender altogether (and then simultaneously excluding the thunderbird process). Unfortunately this shouldn't be a long term solution, and with as long as this has been an issue would be surprised that no one else has seen it. Any other alternatives to completely excluding TB?

I was able to mimic a solution by disabling defender altogether

That isn't a solution.

(and then simultaneously excluding the thunderbird process).

I don't know what that means, and I don't think it's possible at all. You can exclude files that are opened by specific processes from Microsoft Defender Antivirus scans though. Note that these types of exclusions are for files that are opened by processes and not the processes themselves.

So what you should do is to create an exclusion in Defender for the Thunderbird profile folder, so that the Defender real-time scanner will not scan it. https://support.mozilla.org/en-US/kb/profiles-where-thunderbird-stores-user-data#w_how-to-find-your-profile

Unfortunately this shouldn't be a long term solution, and with as long as this has been an issue would be surprised that no one else has seen it.

Creating an exclusion is the long term and only solution. This forum is full with complaints like yours, and the culprit is almost always anti-virus software.

(and then simultaneously excluding the thunderbird process).

I don't know what that means, and I don't think it's possible at all. You can exclude files that are opened by specific processes from Microsoft Defender Antivirus scans though. Note that these types of exclusions are for files that are opened by processes and not the processes themselves.

To exclude the process, under Windows settings goto "Virus & Threat Protection", under "Virus & Threat protection settings" look for "Manage Settings", scroll to bottom for "Exclusions" and choose "Add or remove exclusions". Accept the UAC prompt, click "+Add an exception", you get a dropdown for: File, Folder, File Type, Process. Click process and add "thunderbird.exe"

Yes, that's what I said above, you can only exclude files that are opened by the Thunderbird process and not the process itself.

Click process and add "thunderbird.exe"

Also as said above, you'll have to create the exclusion for the Thunderbird profile folder, and not for the .exe.