E2E. Might not be applicable for remote execution of AI payloads, but it is applicable for most everything else, from messaging to storage.
Even if the client hardware and/or software is also an actor in your threat model, that can be eliminated or at least mitigated with at least one verifiably trusted piece of equipment. Open hardware is an alternative, and some states build their entire hardware stack to eliminate such threats. If you have at least one trusted equipment mitigations are possible (e.g. external network filter).
Is it? I guess this really depends. For E2E storage (e.g. as offered by Proton with openpgpjs), what metadata would be of concern? File size? File type cannot be inferred, and file names could be encrypted if that's a threat in your model.