[Same experience with newest versions of Portable Firefox]
Windows 10 Pro 1909 18363.1139
Since updating to 78.4.0 -- or perhaps since a previous but very recent update -- an 'unkillable' Thunderbird background process is orphaned when exiting the program. Task Manager lists the process as 'Thunderbird.' There's no response to an 'End task' command, the process just sits there. Using the Sysinternals Process Explorer, I get a message "Error terminating process: Access is denied." Trying to restart Thunderbird fails with "Another instance of Thunderbird is already running...." These problems have persisted after updating to 78.4.1 -- just now I had tried to exit TB to update to 78.4.2, but the installer doesn't run either, since it detects the residual process.
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Check your extensions and settings. Also check that some local antivirus or antimalware isn't interfering. This isn't a portable-specific issue on our end. Both exit without issues.
Sometimes, the impossible can become possible, if you're awesome!
Thank you for your attention to the problem. I have tentatively identified and fixed the problem.
I place all my non-system files, including my PortableApps folder, on a virtual drive "derived from" a folder on my local hard drive. The virtual drive had been created using the NET USE command. NET USE has the disadvantage that virtual drives are treated by the system as network locations, even when they actually reside on a locally attached hard drive and even though they have drive letters and function otherwise like proper disks.
It seems as though FF and TB don't play well in such an environment, or don't anymore. The weird thing (and why I'm a little shy about considering the solution definite) is that I've been using this setup all along, and was running FF and TB without any problems until recently when the issues I have reported suddenly appeared. Also, all other portable apps (installed on the same virtual drive) were functioning fine, while FF and TB were not.
At any rate after I today deleted the NET USE virtual drives and created 'replacements' via the SUBST command (persisting them to survive reboots), portable TB and FF are working again, with no changes to their installs.
Virtual drives created with SUBST have a trivial drawback (no volume labels, at least not any easy way to create them) compared to those made with NET USE, but I'm giving up on the latter for this purpose, given the complexities and potential pitfalls of "network" virtual drives.