I struggled for a while with jpg image files not properly opening with the “System Handler” in Thunderbird. Despite changing the file association setting back to “Always ask” to reset it, the wrong application opened the images.
Usually one would just select another application in the list of applications but since it is a Flatpak the sandbox restricts access and none where displaying.
Fiddling around I deleted the second order in the chain where Thunderbird Flatpak searches for the right application to open (after the handlers.json):
rm ~/.var/app/net.thunderbird.Thunderbird/config/mimeapps.list
After a restart the “System Handler” finally opened up the correct application as it was using the third level in the lookup chain, the XDG Desktop Portal, which gracefully forwarded the request to Loupe in this case.