You can clone the profile once, and then delete everything you don't need for testing with the new version.

I was thinking something along the lines of: Create a new profile, inject it with the original profiles' extensions.

Cloning (and deleting) all these files is neither quick nor scalable if e.g. I need to do it again later.

I was thinking something along the lines of: Create a new profile, inject it with the original profiles' extensions.

There is nothing wrong with creating a new profile. I'd not 'inject' extensions from the old profile though. Just install them properly in the new profile if you want to go that route.

Cloning (and deleting) all these files is neither quick nor scalable if e.g. I need to do it again later.

I'm not talking about manually deleting files or folders int he file system. In the new profile, simply delete mail folders or entire accounts not needed for testing extensions in Thunderbird, and to save disk space, if that is a concern. You can keep that test profile indefinitely, so you'd not need to do this again.

I was thinking something along the lines of: Create a new profile, inject it with the original profiles' extensions.

There is nothing wrong with creating a new profile. I'd not 'inject' extensions from the old profile though. Just install them properly in the new profile if you want to go that route.

Unfortunately, I rather do that. I'd rather mimic the normal update path my profile will take, since I had a severely botched update last time.

Cloning (and deleting) all these files is neither quick nor scalable if e.g. I need to do it again later.

I'm not talking about manually deleting files or folders int he file system. In the new profile, simply delete mail folders or entire accounts not needed for testing extensions in Thunderbird, and to save disk space, if that is a concern. You can keep that test profile indefinitely, so you'd not need to do this again.

Not if updating fails, which I believe it will happen.

I'd rather mimic the normal update path my profile will take, since I had a severely botched update last time.

You can prepare the test profile with your existing version of Thunderbird. Then install the new version to a different location, and start it with the test profile.

Not if updating fails, which I believe it will happen.

This is what backups are for. https://support.mozilla.org/kb/profiles-where-thunderbird-stores-user-data#w_backing-up-a-profile

Needless to say, you'd need to create the backup prior to the update.