I have a few different separate scenes that extend each other for the characters. For example, zombie.gd and mummy.gd both extend a basic enemy.gd to add unique abilities to these enemy types. Enemy.gd contains the universal functions and child nodes, such as an Area2Ds for player detection, an Area2D for hit collision, etc.
The main game scene is a collection of other instanced scenes inherited from other files, such as level.tscn, gui.tscn, and several enemies from zombie.tscn and mummy.tscn. The player's character is being added programmatically, since I plan to allow multiple different character classes.
The player is still able to interact with the enemy mobs, hitting and killing them off enemies. It's just the enemies themselves do not act on their own anymore (chasing players or attacking when the player is near) after changing the scenes transition from the lobby the the main game scene.
I don't think this should be a layer or mask configuration issue, as I can switch the scene transition back to
get_tree().change_scene_to(main) and all of my enemies start chasing the player and attacking them again.