Does this happen when printing with removable storage (SD card or flash drive)?

Based on its construction, I would recommend starting with the Ender 5 Profile and updating the build volume at Edit Process Settings > Gcode. Since essentially everything is the same except the size, the settings in this profile should work well on it.

Yes, you can contact support to send you the latest profile.

If you have your detail parts as separate STLs, you can assign them a different extruder with completely different settings. If it is just one model, there is no way to specify, say, threads to be printed with the second extruder. You can set the infill to print with the second extruder, and use the...

Given that every printer is different, I would recommend using our supports article to learn more about Simplify3D supports and how to tune them for easier removal: https://www.simplify3d.com/support/arti ... tructures/

If you change your Internal Thin Wall Type in the Advanced tab to "Allow single extrusion fill" these lines should get filled in better with a dynamically varying extrusion.

Yep, and you can read in more detail about this process in this post: viewtopic.php?f=8&t=5977&p=25950#p25947

As Doug said, lowering the resolution will help. If you Open the Support Generation tool and Generate Automatic Supports, you can see that the larger pillars are intersecting that small hole in order to be able to support the surface above the void. Lowering the Support Pillar Resolution to 1mm mean...

For future reference, this is caused by the Lower Vertical Separation Layers in the Support tab being set to 1. This prevents the supports from adhering too strongly to your part, but can be set to 0 to get the supports to print directly on the previous layer.

If you go to File>Save Factory File As... you can save off the factory file that includes all of your settings and your model setup. This is an easy way to share entire projects!