Did some searching. Lots of people have this issue where cruise only works in 4th after doing a manual swap. The computer seems to be calculating what gear the transmission is in by looking at engine speed vs. vss. If the computer can't find a matching ratio, you don't get cruise. The only way it works, is if your manual transmission has the same gear ratios as whatever transmission segment you swapped in (ZF6, nv3500, etc...). All of those transmissions have a 1:1 direct ratio, so the PCM sees that as valid, and allows cruise to work.
The general consensus seems to be that there is another set of transmission gear ratio inputs in the transmission or engine side of things that HPTuners doesn't expose that needs to be changed.
A workaround seems to be setting the vehicle for an automatic transmission. That seems to get cruise to work again.