While my mixer/audio interface is different (I use a Behringer XR18), I suspect your are experiencing issues similar to what I did.
Make sure that the USB returns (not sure what that’s called on the Mackie, but it’s the channels that come back over USB from your DAW for the master channels) are matched to the DAW.
In my setup, Cubasis comes back via USB 1/2 for master channels 1/2. When I set that on the mixer, I have audio.