(For persistent Tails.)
(But we should always default to POP therefore this is good.)
Possible. I don’t know how often that folder is parsed. Only first start vs every start. Perhaps even a setting influences this.
Fresh snapshot is a bit too much effort. Can be easier.
In abstract terms “Any previous state of Thunderbird must be deleted.”
“If it requires a fresh snapshot then you don’t know all the places yet where the application stores state.”
Exceptions  (which don’t apply here) aside, the only place where non-root applications can write data is the home folder. 
In practical terms: terminate thunderbird + delete thunderbird user data folder.
WARNING: deletes all Thunderbird user data
rm -r .thunderbird
In case you don’t know what the user data folder is… How would I know where XFCE stores any settings? I don’t. I am not an oracle either. Even if I’d know, I’d forget in a year from now.
abstract: “Make a snapshot of the home folder and compare before/after first start of application.”
practical: I recommend to Put home folder under Git Version Control.
 Exceptions would be suid and sudoers exceptions which there is no need for in case of browser / mail client user data.
 And /tmp and perhaps folders chown’ed to user during package installation but any sane design won’t persist settings from there