Mules are human enemies afflicted with a mysterious illness that drives them to steal cargo from unwary porters. They will then take their finds back to their camps located in various locations around the game world. Stolen goods are then stored in mule postboxes.
Use the surveying sensor
Scan the area using the sensor to detect any nearby mules. You will also be able to detect the cargo a mule is currently carrying which might be useful in your mission.
Reduce your weight before engaging
Having heavy cargo will hinder your mobility. You can also drop your cargo if you get hit, damaging your package in the process. Try to store some of your cargo in a locker before engaging mules.
Bring dummy cargo
Mules are driven by their illness to take any kind of package, regardless of its contents or if it has anything inside at all. To exploit this, you can load dummy cargo on your back with nothing inside.
Stealth is important
Taking out mules without being seen is the best way to deal with them. Approach them from behind and bind them with the strand to knock them out with the least amount of effort.
Mules can be knocked out in a single blow
It is possible to render a mule unconscious with a single strike. You can press the □ button to land a hit, though you will be at risk of a counterattack. Taking damage yourself can cause your cargo to drop and get damaged.
Tackle mules when they are guarding
Mules will sometimes adopt a guarding stance when you are fighting with them. You can, however, break their defenses by tackling them. Note that tackling will expend stamina. You also will not be able to perform the move if your hands are holding onto some cargo.