This game shines a strong light on various ways humans mistreat animals, including whaling, game hunting, slaughterhouses, forced captivity of wild animals, abandonment, and more.
Not on camera, but all animals in the world are extinct at the start of the game, and some dead bodies are seen: a dog, a pig, an eagle, a polar bear, a deer, a whale, a shark, and a hive's worth of giant bees.
Bodies of multiple animals can be seen throughout the game. They are effectively fossilised and no gore can be seen, but the causes of most of their deaths are extremely apparent and upsetting (bullet holes, harpoons in their body, exposed ribs, etc.)
Not on-screen, but one of the spirits of extinct animals you can collect is that of a horse, showing that they have all passed by the time of the game.
The main character seems to be a child and goes through some bad stuff, much of it encouraged by her parental figure. There are also many statues throughout the game showing children in bad situations, such as being threatened, falling to their deaths, etc. Finally, there are child enemies who must be defeated, but the game says that they don't die; their hearts are just redeemed.
A couple of the animal spirits which can be found are spiders. This causes small, ghostly spiders to appear in various places in the game. They are harmless and friendly to the player character. I don't recall seeing any move around, instead remaining stationary.
One of the sets of memories shows a scientist developing a new prosthetic arm, which is eventually presented to a young boy who only has one arm. Amputation is not directly shown, but is alluded to.
One of the main ways enemies attack in the game is by grabbing and holding onto the player character. There is also a level where the character has to avoid hunters and their traps, and stepping into a beartrap or snare will cause her to become trapped until she can free herself.
There are multiple times when an enemy will hide and watch you, then jump out and attack. There is also a section where the player character takes the role of a deer being hunted, having to stay out of the light or risk being shot.
Less substance addiction, and more a heavily implied addiction to television throughout the Power Plant stage. Some humans are shown becoming completely listless because of this, and others are shown putting themselves or others in danger because of it.