What does the Torah mean when it writes "But (Ach), your blood, of your souls, I will seek (avenge)"?
Rashi: The Pasuk is referring to someone who commits suicide, whether by literally spilling his own blood or by strangling himself. 1
Ramban: It means that HaSh-m will take to task someone who spills somebody else's blood, which is synonymous with his soul. The Torah is explaining here that one is Chayav Misah only for killing a person, but not for wounding him. Even though one is not Chayav for spilling the blood of an animal, one is Chayav for that of a human-being, because his blood is his soul, which is more valuable than that of an animal.
Da'as Zekenim, citing Bereishis Rabah: "Ach" excludes Mesiras Nefesh at a time of decrees. If one fears lest he not stand up against the temptation, he may kill himself, like Shaul, lest he be unable to bear great affliction.
The Ramban also cites this Chazal, but he also presents the simple explanation of the Pasuk, as he often does.
Why does the Torah find it necessary to warn the animals not to kill human-beings?
Rashi: This was because, due to their abundant sins, the people of that generation had been given over to the wild animals as fodder.
Ramban: It is also possible that the Torah is telling us here that, although from now on, people were allowed to slaughter animals, and an aura of killing descended upon the world, as a result of which the animals were now permitted to kill each other. Nevertheless, HaSh-m placed in their hearts a fear of man, and they will therefore be taken to task for killing him. 1
In fact, the Ramban concludes, the reason that the Torah inserts the Isur of murder here, is because it permitted Shechitah of animals.
Since when are animals subject to reward and punishment?
Seeing as a murderer is liable to receive the death-penalty at the hands of the judges (as the Torah will specifically state in the next Pasuk), why does the Torah write that HaSh-m will punish him?
Rashi: This Pasuk discusses when there are no witnesses, and the next Pasuk discusses when there are witnesses.
What does the Torah mean when it writes that HaSh-m will seek the soul of a man from his brother?
Rashi: It says this with reference to someone who kills his "brother" (towards whom he bears no hatred), and who will be made to go into exile 1 - in the event that he does not do Teshuvah.
Seforno: Initially, HaSh-m will set out to rescue a man from the clutches of a wild animal or from those of a fellow-human-being. If however, he is not worthy of being rescued, then He will take the soul of the latter (his brother) 2 , but not of the former (an animal). 3
Ramban: The Pasuk may also teach us that a murderer will not escape, because, should the need arise, HaSh-m will send after him wild animals and people, who will get him by hook or by crook.
Like the Mashal cited by Rashi (to Shemos 21:18) about two people who killed, one b'Mezid, the other, b'Shogeg.
This is because he has taken the life of a man who is made in the image of G-d, as the next Pasuk explains.
רש"י: מהשופך דם עצמו: כיצד משמע כך בפסוק?
גור אריה: "אך" בא למעט מהכלל הראשון, ולכן פירש שבא לאסור נטילת נשמת אדם [אחר שהתיר הריגת בהמה].
רש"י: אף החונק עצמו: קשה שאין לחלק בין חניקה לשאר מיתות?
גור אריה: נראה שגירסא זו משובשת.