I mean it would make way more sense to use one of the many messengers that explicitly use TOR like Cwtch or Briar.
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Yes and federation works. The caveat is that since Matrix s2s de facto mandates TLS certs, you'll need to use self-signed certs as well as accept them from other onion peers. I've been aware of some more involved setups where a server name on the clearnet can be manually mapped to its Tor onionsite as well.
Beyond that, c2s is just a simple HTTP service, and most clients should support it assuming they have a way to hop on Tor (Orbot, SOCKS5 proxy etc)
I think it's possible to run anything that can be run over a network over Tor. Tor can be set up as a proxy for any piece of software.
or just use SimpleX
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