Well, doing this on top of a single language is more feasible, however the Python-Lisp pair is still not the best choice due to Python's strict semantics of separation between statements and expressions: when you generate an AST from Lisp, you'd have some sorta verbose shims in place of Lisp's expression-ic statements—precisely ones that Hy now creates. And vice versa, a coder's normal Python might not map cleanly to Hy.

If you're free to invent the languages in the first place, it would be kinda trivial to make several with the same semantics but different superficial syntax—basically just substitute one bunch of characters for another, no need to go via AST even. And these languages can then be transpiled to a single language of your choice, be that Python or JVM bytecode—if the semantics are made to be close enough.