>I don't really see how it's possible to mitigate client compromise.

You could of course offload plaintext input and output along with cryptographic operations and key management to separate devices that interact with the networked device unidirectionally over hardware data diodes, that prevent malware from getting in or getting the keys out.

Throw in some v3 Onion Services for p2p ciphertext routing, and decent ciphersuite and you've successfully made it to at least three watch lists just by reading this. Anyway, here's one I made earlier https://github.com/maqp/tfc