That depends on how you set up your combatants to handle this.
E.g. the 2D grid battle tutorials handle the orientation using movement direction. See this attack schematic tutorial as an example, it sets the move direction to face the target.
Another way is to handle orientation by rotating on the Z axis and forwarding that information to the animator controller to play the correct animation based on it. E.g. having the root game object of a combatant rotate and the sprite on a child object with a Face Camera component to keep it upright and facing the camera at all times.