Thunderbird keeps a full copy of your mailbox on the Mac, and deleted mail until you compact

Thunderbird is usually set to keep a copy of every message on the Mac, so you can read mail offline. With a large IMAP account, that copy can be tens of GB. It also does not free space from deleted mail until folders are compacted.

Measure it

du -sh ~/Library/Thunderbird/Profiles/*
du -sh ~/Library/Thunderbird/Profiles/*/ImapMail/* 2>/dev/null | sort -h | tail
du -sh ~/Library/Caches/Thunderbird 2>/dev/null

1. Compact folders

Deleting an email marks it deleted, but the space stays inside the folder file until compacting. Choose File, Compact Folders. Thunderbird can also do it automatically in Settings, General, Network and Disk Space.

2. Stop keeping everything offline

For each account, open Account Settings, Synchronization and Storage. Untick Keep messages for this account on this computer, or keep offline copies only for recent messages or selected folders. Old mail stays on the server and downloads when you open it.

3. Clear the cache

In Settings, General, Network and Disk Space, click Clear Now next to the cache size. It rebuilds on its own.

4. Attachments

Large attachments in Sent and Inbox are often most of it. Search for large messages and delete them, or detach attachments to a folder you can archive.

Apple Mail's equivalent is in Mail local copies.